The objective of the current project is to develop new drug therapies to treat cognitive dysfunction associated with Alzheimer's disease. The goal is to treat symptoms such as memory impairment but also to delay the onset of the brain dysfunction that underlies this cognitive decline. The proposed experiments aim to demonstrate the efficacy of a novel muscarinic M1-specific agonist (VU0364572) in treating hippocampal dysfunction in a rat model of Alzheimer's disease. The approach will focus on in vivo electrophysiological recordings of many individual hippocampal neurons as a sensitive assay of memory functioning. In addition, the proposed experiments aim to demonstrate the efficacy of VU0364572 in delaying the onset of memory impairments and brain pathology in a rat model of Alzheimer's disease. Over the two- year period, the proposed experiments are expected to contribute to the training of one graduate student and two undergraduate students.